Osteoclastic bone resorption is dependent upon cell-matrix recognition. This process is mediated by the integrin αvβ3 whose expression is enhanced, in avian osteoclast precursors, by bone-seeking steroids. The purpose of this study was to determine if bone-modulating cytokines impact on αvβ3 expression by mouse marrow macrophages (BMMs), known to differentiate into osteoclasts. Of the cytokines tested. Interleukin-4 (IL-4) is most effective in increasing β3 mRNA levels by a mechanism involving transactivation of the β3 gene. Moreover, IL-4 augmented β3 mRNA is mirrored by plasma membrane appearance of αvβ3. As IL-4 induces β3 and not αv mRNA, the β3 chain appears to regulate surface expression of the heterodimer. The functional significance of IL-4-induced αvβ3 is underscored by the fact that, while attachment to fibronectin is unaltered, treatment of BMMs with the cytokine enhances αvβ3-mediated binding to vitronectin 5-fold. Expression of this heterodimer by BMMs driven along a non-osteoclastic lineage suggests αvβ3 may play a role in the inflammatory response of macrophages.